{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:28:54Z","timestamp":1792009734103,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203972\/Z\/16\/A"],"award-info":[{"award-number":["203972\/Z\/16\/A"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Synapse degeneration in Alzheimer's disease (AD) correlates strongly with cognitive decline. There is well\u2010established excitatory synapse loss in AD with known contributions of pathological amyloid beta (A\u03b2) to excitatory synapse dysfunction and loss. Despite clear changes in circuit excitability in AD and model systems, relatively little is known about pathology in inhibitory synapses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here human postmortem brain samples (<jats:italic>n<\/jats:italic>\u00a0=\u00a05 control, 10 AD cases) from temporal and occipital cortices were examined to investigate whether inhibitory synapses and neurons are lost in AD and whether A\u03b2 may contribute to inhibitory synapse degeneration. Inhibitory neurons were counted in all six cortical layers using stereology software, and array tomography was used to examine synapse density and the accumulation of A\u03b2 in synaptic terminals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differing inhibitory neuron densities were observed in the different cortical layers. The highest inhibitory neuron density was observed in layer 4 in both brain regions and the visual cortex had a higher inhibitory neuron density than the temporal cortex. There was significantly lower inhibitory neuron density in AD than in control cases in all six cortical layers. High\u2010resolution array tomography imaging revealed plaque\u2010associated loss of inhibitory synapses and accumulation of A\u03b2 in a small subset of inhibitory presynaptic terminals with the most accumulation near amyloid plaques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inhibitory neuron and synapse loss in AD may contribute to disrupted excitatory\/inhibitory balance and cognitive decline. Future work is warranted to determine whether targeting inhibitory synapse loss could be a useful therapeutic strategy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15043","type":"journal-article","created":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T08:11:19Z","timestamp":1627719079000},"page":"1311-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer's disease"],"prefix":"10.1111","volume":"29","author":[{"given":"Hatice","family":"Kurucu","sequence":"first","affiliation":[{"name":"University of Edinburgh Centre for Discovery Brain Sciences and UK Dementia Research Institute  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00ed","family":"Colom\u2010Cadena","sequence":"additional","affiliation":[{"name":"University of Edinburgh Centre for Discovery Brain Sciences 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